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An extracellular role for calmodulin-like activity in cell proliferation
G Crocker1, R A Dawson, C H Barton
1Department of Medicine, University of Sheffield, Northern General Hospital, U.K.
The Biochemical Journal
|August 1, 1988
Summary
Extracellular calmodulin influences cell division in K562 leukaemic lymphocytes. This protein modulates DNA synthesis and cell proliferation, suggesting a novel extracellular mechanism regulating mitosis.
Area of Science:
- Cell Biology
- Biochemistry
- Cancer Research
Background:
- Calmodulin is a key intracellular calcium-binding protein.
- Its role in extracellular signaling and regulation of cell proliferation is not well understood.
Purpose of the Study:
- To investigate the role of extracellular calmodulin in modulating DNA synthesis and cell proliferation in K562 human leukaemic lymphocytes.
- To determine if K562 cells secrete a calmodulin-like protein.
Main Methods:
- Addition of purified calmodulin to K562 cell cultures.
- Detection and quantification of calmodulin-like activity in cell-conditioned media.
- Inhibition of extracellular calmodulin activity using antagonists and antibodies.
- Measurement of [3H]thymidine uptake to assess DNA synthesis.
Main Results:
- Extracellular calmodulin modulated DNA synthesis and proliferation in K562 cells in a density-dependent manner.
- K562 cells secreted a protein biochemically indistinguishable from calmodulin into conditioned media.
- Peak extracellular calmodulin levels preceded DNA synthesis in synchronized cells.
- Inhibition of extracellular calmodulin activity significantly reduced DNA synthesis.
Conclusions:
- Calmodulin or a closely related protein can influence mitosis via an extracellular mechanism.
- Extracellular calmodulin may play a regulatory role in cell proliferation of leukaemic lymphocytes.